title: Neonatal exposure to genistein ameliorates high-fat diet-induced non-alcoholic steatohepatitis in rats.
abstract: Non-alcoholic steatohepatitis (NASH) is becoming a prevalent disease in developing countries with no effective therapy. Isoflavones such as genistein have been shown to prevent NASH in a rat model, but the effects of neonatal exposure to genistein on lipid metabolism have been rarely studied. In the present study, three doses of genistein (30, 300 or 1200 μg/rat per d) were injected (subcutaneously) into neonatal male Sprague-Dawley rats at postnatal days 1-5. After weaning, these rats were allowed free access to a high-fat diet for 6 weeks. The results demonstrate that NASH was induced by high fat feeding in the control rats, whereas genistein-treated rats displayed smaller body weight, and lower hepatic inflammation and steatosis. The mid dose of genistein was most effective. Neonatal exposure to genistein also resulted in a lower incidence of apoptotic cells in the liver. Additionally, neonatal genistein-treated rats showed lower hepatic expression of fatty acid synthase and sterol regulatory element-binding protein-1, but higher expression of PPARα, indicative of lower rates of lipid synthesis and higher rates of β-oxidation. These results indicate that neonatal treatment with genistein has a prolonged effect on hepatic lipid metabolism that is maintained post-weaning, offering a potential approach for the prevention of hepatic steatosis and NASH.
authors.affiliation: State Key Laboratory of Animal Nutrition, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, People's Republic of China.
authors.forename: Chengfei
authors.initials: C
authors.lastname: Huang
authors.forename: Xubai
authors.initials: X
authors.lastname: Qiao
authors.forename: Bing
authors.initials: B
authors.lastname: Dong
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001835:Body Weight; D004041:Dietary Fats / Q000009:adverse effects*; D019587:Dietary Supplements; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005786:Gene Expression Regulation; D019833:Genistein / Q000008:administration & dosage*; D022781:Hepatocytes / Q000187:drug effects; D008099:Liver / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D004041:Dietary Fats; D019833:Genistein